Studies in the coming year will focus on: (1) Mechanism of action of phenolphthalein, (2) Transport studies in brush border and basolateral vesicles aimed at demonstrating coupled NaC1 influx mechanisms and how these mechanisms are perturbed by antidiarrheal and cathartic compounds. Studies on phenolphthalein's effect on both in vivo and in vitro water and electrolyte transport in both the jejunum and colon of cynomolgus monkeys will be performed using the Ussing chamber and perfusion techniques. The data thus obtained will shed light on the mechanisms of the cathartic effect of this drug in primates. Techniques for isolating and purifying rabbit ileal brush border and basolateral membranes will be perfected. While the techniques are being worked out in this species, we will continue transport studies in our preparation of rat intestinal brush border and basolateral membranes. We hope to demonstrate coupled NaC1 influx mechanisms. If found, we will determine the effect of various antidiarrheal compounds (salicylate, gallate, nicotinate, galacturonate) and various diarrheal compounds (furosemide and phenolphthalein), on that ion transport mechanism. These studies should aid our understanding of normal electrolyte transport by intestine and how these normal mechanisms are perturbed by clinically important drugs.